2. Academic Validation
  3. Age-associated decline of Coenzyme A leads to intestinal stem cells dysfunction via disturbing iron homeostasis

Age-associated decline of Coenzyme A leads to intestinal stem cells dysfunction via disturbing iron homeostasis

  • PLoS Genet. 2025 May 30;21(6):e1011704. doi: 10.1371/journal.pgen.1011704.
Zhiming Liu 1,  Gang Du 2 3,  Yi Chen 4,  Haiyang Chen 1
Affiliations

Affiliations

  • 1 West China Centre of Excellence for Pancreatitis, and Laboratory of Metabolism and Aging, Frontiers Science Center for Disease-related Molecular Network, State Key Laboratory of Respiratory Health and Multimorbidity and National Clinical Research Center for Geriatrics, West China Hospital, Sichuan University, Chengdu, China.
  • 2 Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts, United States of America.
  • 3 Program in Cellular and Molecular Medicine, Boston Children's Hospital, Boston, Massachusetts, United States of America.
  • 4 Division of Gastrointestinal Surgery, Department of General Surgery, West China Hospital, Sichuan University, Chengdu, Sichuan, China.
PMID: 40446021 DOI: 10.1371/journal.pgen.1011704
Abstract

The decline in adult stem cell performance is closely linked to tissue malfunction and the rising incidence of age-related diseases. To investigate the molecular basis of these impairments, our screening strategy identified reduced activity in the pantothenate/coenzyme A (CoA) pathway within aged ISCs. Furthermore, exogenous CoA supplementation restructured ISC metabolic pathways, reversing age-induced hyperproliferation and intestinal dysfunction, and thus extending Drosophila lifespan by curbing excessive iron accumulation in ISCs. These findings uncover a new mechanism of stem cell aging and propose that pantothenate and CoA could be potential therapeutic targets for treating age-related diseases and enhancing healthy aging in humans.

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